Variant 4-75961307-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018115.4(SDAD1):c.1183A>G(p.Ile395Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000412 in 1,457,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SDAD1
NM_018115.4 missense, splice_region

Scores

Splicing: ADA: 0.4139

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

Variant links:

Genes affected

SDAD1 (HGNC:25537): (SDA1 domain containing 1) Predicted to be involved in ribosomal large subunit biogenesis and ribosomal large subunit export from nucleus. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SDAD1 links:

SDAD1 (HGNC:):

SDAD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3718567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDAD1	NM_018115.4 linkuse as main transcript	c.1183A>G	p.Ile395Val	missense_variant, splice_region_variant	15/22	ENST00000356260.10	NP_060585.2	Q9NVU7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDAD1	ENST00000356260.10 linkuse as main transcript	c.1183A>G	p.Ile395Val	missense_variant, splice_region_variant	15/22	1	NM_018115.4	ENSP00000348596.5		Q9NVU7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1457494

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.1183A>G (p.I395V) alteration is located in exon 15 (coding exon 15) of the SDAD1 gene. This alteration results from a A to G substitution at nucleotide position 1183, causing the isoleucine (I) at amino acid position 395 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

0.093

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.90

N;N

REVEL

Benign

0.099

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.0090

B;B

Vest4

0.39

MutPred

0.67

Loss of ubiquitination at K399 (P = 0.1322);.;

MVP

0.33

MPC

0.058

ClinPred

0.82

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.41

dbscSNV1_RF

Benign

0.38

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over